Water → tert-Butyl [(3S)-2-oxooxetan-3-yl]carbamate

Temperature

-45 °C

Methyl azodicarboxylate-derivatized resin (6.55 g, 4.0 meq) was swollen briefly (15 min) in dry THF (100 mL). The stirred suspension of beads was cooled to -45° C. and BOC-L-serine (473.5 mg, 2.30 mmol) was added. To this mixture at -45° C. was added a solution of triphenylphosphine (1.06 g, 4.0 mmol) in THF (5 mL) dropwise over 10 min. The suspension was stirred 30 min at -45° C., allowed to warm slowly to 0° C. over 1 h, and stirred 2 h further. H2O (36μL) was added as a precautionary quench and the resin was filtered and washed with THF (2 ×100 mL) and CH3CN (100 mL). The filtrate and washings were pooled and concentrated in vacuo at 35° C. The residue was flash chromatographed (35% EtOAc/hexane) to yield 242.7 mg (56%) of BOC-L-serine β-lactone: mp 119.5-120.5° C (dec); [α]25 -26.7 (±0.2)°(c 1.0, CH3CN); IR [Fluorolube (trademark) mull](CH2Cl2 cast) 3358 (s), 1836 (s), 1678 (vs), 1532 (s), 1291 (m), 1104 (s) cm-1 ; ε1847 cm-1 (0.1 mm KBr, THF or CH3CN) 0.34 mL mg-1 mm-1, 64 M-1 ; mm-1 ; 1H NMR (200 MHz, CD2Cl2) δ5.53 (br s, 1H, NH), 5.05 (dd, 1H, 8, 6 Hz, CH), 4.47 (~d, 2H, 6 Hz, CH2O), 1.47 (s, 9H, tert-Bu); 13C NMR (50.32 MHz, CD2Cl2) ≃170.0 (s), 155.1 (s), 81.5 (s), 66.6 (t), 59.9 (d), 28.2 (q); Anal. Calc. for C8H13NO4 : C, 51.33; H, 7.00; N, 7.48. Found: C, 51.04; H, 6.97; N, 7.42; EI--MS: 188.0929 (MH+, 188.0923 calcd.); CI--MS (NH3) 205 (M+NH+), 392 (2M+NH4+).

1. additionThe stirred suspension of beads
2. temperatureto warm slowly to 0° C. over 1 h
3. stirringstirred 2 h further
4. customa precautionary quench
5. filtrationthe resin was filtered
6. washwashed with THF (2 ×100 mL) and CH3CN (100 mL)
7. concentrationconcentrated in vacuo at 35° C
8. customchromatographed (35% EtOAc/hexane)

ORD record

ord-21b13a69485342a695b55427774c3dc3

Source dataset

uspto-grants-1990_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04960832